Regulation of breathing in newborns at high altitude

Resting respiratory parameters and respiratory responses to acute changes in end-tidal O2 and CO2 pressure (PETO2 and PETCO2) were investigated in Peru in 23 newborn and 4 older infants at 3.850 m and in 13 newborns at 800 m. The study was done with the subjects asleep in a thermoneutral environment. The transient increase in ventilation in both high- and low-altitude newborns was followed by a decrease in response to acute hypoxia. During hyperoxia the two groups showed a slight but not clearly significant decrease in ventilation, whereas older high-altitude infants showed a sustained decrease. All subjects showed a prompt and clear response to CO2 inhalation during hyperoxia. We conclude that ventilatory peripheral chemoreflex is not fully developed in newborns regardless of altitude. The weak link in the reflex arc may reside in the afferent component because CO2 response was not impaired. Since hypoxic response became persistent in older infants its blunting in adult high-altitude natives is not a legacy of newborns.     

Inhibition of growth and development of tobacco hornworm (Lepidoptera: Sphingidae) larvae by cyromazine

When fed to larvae of tobacco hornworm, Manduca sexta (L.), cyromazine strongly inhibited normal growth and development. Depending on the dose or period of feeding, symptoms were cuticular melanization, swellings in intersegmental regions, cuticular lesions, rupture of the body wall, and death. At greater than 10 ppm, cyromazine in the diet initiated symptoms in fifth instars, whereas greater than 20 ppm induced symptoms which led to death during the instar or at molting. The ratio of chitin to larval body weight in both cyromazine-exposed and control fifth instars increased slightly from ecdysis to 42 h. However, this ratio did not differ between the two groups, indicating that cyromazine had no immediate or direct effect on chitin production. When cyromazine was ingested by fifth instars, it was excreted rapidly, and a small amount (less than 5%) was metabolized to melamine. The amount of cyromazine found in the hemolymph remained relatively constant during the feeding period, whereas the amount present in the body wall increased with time and was localized in the KOH-soluble fraction. Cyromazine may inhibit growth or expansion of the body wall (or both) sufficiently to prevent normal internal growth, producing the observed symptoms and leading to abnormal development.     

Comparison between in vivo and in vitro cutaneous penetration of fenvalerate in tobacco budworm (Lepidoptera: Noctuidae)

In vivo and in vitro penetration of fenvalerate were compared in the 3-d-old fifth-instar tobacco budworm, Heliothis virescens (F). In the in vitro studies, a piece of cuticle was excised and mounted on a diffusion cell, and the amount of radioactivity present in the cuticle and medium was determined at various time intervals. At 24 h, approximately 7.4% of the dose was located in the cuticle, whereas only 1.6% actually penetrated. In the in vivo studies, approximately 7.4% of the radioactivity was recovered from the body after cuticular wash.     

Multiple receptor proteins for sweet taste inDrosophila discriminated by papain treatment

Summary Treatment of the labellar chemosensory setae of the fruit fly,Drosophila melanogaster, with 0.1 % papain for 3 min induced a complete elimination of the taste nerve response to fructose (Fig. 1). Responses to other sugars examined were not affected (Table 1). Responses to 20 mM LiCl and 0.1 M NaCl also remained unchanged by the treatment. The experiment on the time-dependency of the papain treatment showed a clear difference in the proteasesensitivity between the response to fructose and to glucose and sucrose (Fig. 2). The treatment with 0.005% trypsin for 3 min produced the same results. The response to fructose which was eliminated with the papain treatment, was restored after 3 hrs. These findings reveal the presence of a specific receptor site for fructose and its protease-sensitive nature and suggest the involvement of multiple receptor proteins in the sugar receptor ofDrosophila.We thank Dr. A. Shiraishi for valuable suggestions for electrophysiological recordings. This work was supported in part by a Grant-in Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan.     

Phosphotyrosine phosphatase: a novel phosphatase specific for phosphotyrosine, 2'-AMP and p-nitrophenylphosphate in rat brain

A unique phosphatase that selectively hydrolyzed phosphotyrosine and 2'-AMP at alkaline pH and p-nitrophenylphosphate at neutral pH was isolated from a cytosolic fraction of rat brain. The purified enzyme appeared homogenous on SDS-polyacrylamide gel electrophoresis and its molecular weight was estimated to be 42,000. The molecular weight of the native enzyme was 45,000 as determined by molecular sieve chromatography. These findings indicate that the native enzyme is a monomer protein. At pH 8.6, the enzyme hydrolyzed L-phosphotyrosine, D-phosphotyrosine, 2'-AMP, p-nitrophenylphosphate, 3'-AMP, 2'-GMP, and 3'-GMP; the ratio of its activities with these substrates was 100:96:115:68:39:25:16. Its Km values for L-phosphotyrosine, 2'-AMP, and p-nitrophenylphosphate were 0.8 X 10(-4) M, 1.4 X 10(-4) M, and 1.7 X 10(-4) M, respectively. At pH 7.4, the enzyme hydrolyzed p-nitrophenylphosphate, L-phosphotyrosine, and D-phosphotyrosine; the ratio of its activities with these compounds was 100:17:17, and its Km values for L-phosphotyrosine and p-nitrophenylphosphate were 1.8 X 10(-4) M and 2.0 X 10(-4) M, respectively. The enzyme activity was dependent on Mn2+ or Mg2+, and was strongly inhibited by 5'-nucleotides, pyrophosphate, and Zn2+. The enzyme was not sensitive to inhibitors of some well-characterized phosphatases such as NaF, molybdate, L(+)tartrate, tetramisole, vanadate, and lithium salt. The physiological role of the enzyme is discussed with respect to its activities toward phosphotyrosine, 2'-AMP, and p-nitrophenylphosphate.     

Biosynthetic gene cluster identification and biological activity of lucilactaene from Fusarium sp. RK97-94

ABSTRACT

We identified the biosynthetic gene cluster for lucilactaene, a cell cycle inhibitor from a filamentous fungus Fusarium sp. RK 97–94. The luc1 knockout strain accumulated demethylated analogs, indicating the involvement of Luc1 methyltransferase in lucilactaene biosynthesis. Lucilactaene showed potent antimalarial activity. Our data suggested that methylation and ether ring formation are essential for its potent antimalarial activity.     

Genetic dimorphism in the taste sensitivity to trehalose inDrosophila melanogaster

Summary A quantitative behavioral assay was developed for the measurement of taste responses to sugars inDrosophila. The amount of the intake of a sugar solution was measured colorimetrically after homogenization of flies which had consumed sugar solutions mixed with a food-dye. A two-choice method was utilized to determine the taste sensitivity to sugars. Two kinds of sugar solutions were marked with either blue or red food-dye and placed alternately in the wells of a micro test plate. Flies were allowed to choose between the two sugar solutions. By classifying and counting the coloured flies, the relative taste sensitivity could be determined. Employing these methods, a genetic dimorphism in the taste sensitivity to trehalose was found among some laboratory strains ofDrosophila melanogaster. No difference in the taste sensitivity to glucose, fructose and sucrose was found between the trehalose high-sensitivity (T-1) and the low-sensitivity (Oregon-R) strains. Trehalose concentration equivalent to 2 mmol/1 sucrose, in terms of stimulating activity, was 57 mmol/1 inOregon-R and was 10 mmol/1 inT-1. Genetic analysis showed that theTre gene, whose locus is closely linked tocx (13.6) on theX chromosome, is responsible for the difference in the taste sensitivity to trehalose.     

N-terminal [Glu]3 moiety of γ-glutamyl peptides contributes largely to the activation of human calcium-sensing receptor,a kokumi receptor

ABSTRACT

γ-glutamyl peptides have been suggested to impart kokumi properties to foods by activating human calcium-sensing receptor (hCaSR). In this study, the relationship between γ-glutamyl peptide structure and hCaSR activity was systematically analyzed using γ-[Glu]_(n=0-4)-α-[Glu]_(n=0-3)-Tyr. Our results suggest that N-terminal [Glu]₃ moiety is very important for hCaSR activities of γ-glutamyl peptides.